Results 111 to 120 of about 1,596 (140)

Nipping disease in the bud: nSMase2 inhibitors as therapeutics in extracellular vesicle-mediated diseases

Drug Discovery Today, 2021
Extracellular vesicles (EVs) are indispensable mediators of intercellular communication, but they can also assume a nefarious role by ferrying pathological cargo that contributes to neurological, oncological, inflammatory, and infectious diseases. The canonical pathway for generating EVs involves the endosomal sorting complexes required for transport ...
Norman Haughey, Barbara Stauch Slusher, Takashi Tsukamoto   +2 more
exaly   +3 more sources

nSMase2 activation and trafficking are modulated by oxidative stress to induce apoptosis [PDF]

Biochemical and Biophysical Research Communications, 2006
We have previously shown that accumulation of ceramide, triggered by hydrogen peroxide (H(2)O(2)), induces apoptosis of human airway epithelial (HAE) cells. Under oxidant exposure, a lung sphingomyelinase (SMase) is activated and displays continued ceramide generation and pro-apoptotic signaling, thus leading to the pathological apoptosis that causes ...
Tzipora Goldkorn
exaly   +3 more sources

Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP

Journal of Medicinal Chemistry, 2022
Extracellular vesicles (EVs) can carry pathological cargo and play an active role in disease progression. Neutral sphingomyelinase-2 (nSMase2) is a critical regulator of EV biogenesis, and its inhibition has shown protective effects in multiple disease states.
Arindom Pal, Sadakatali Gori, Seung-wan Yoo, Ajit G. Thomas, Ying Wu, Jacob Friedman, Lukáš Tenora, Harshit Bhasin, Jesse Alt, Norman Haughey, Barbara S. Slusher, Rana Rais   +11 more
openaire   +2 more sources

ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation [PDF]

Journal of Lipid Research, 2016
Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level.
Christopher Clarke, Yusuf Hannun
exaly   +4 more sources

nSMase2 inhibition reduces tau propagation in Alzheimer’s Disease mouse models

Alzheimer's & Dementia, 2022
AbstractBackgroundAlzheimer’s Disease (AD) is the most common form of dementia worldwide and is characterized by progressive neurodegeneration and cognitive decline, putatively driven by the accumulation Amyloid‐b and hyperphosphorylated Tau. Clinical trial successes focusing on reducing Amyloid‐b plaque levels in patient brains have been modest ...
Carolyn Tallon, Benjamin J Bell, Medhinee Malvankar, Ajit G Thomas, Seung Wan Yoo, Arindom Pal, Ying Wu, Kaleem Coleman, Tawnjerae R Joe, Anjali Sharma, Erden Eren, Xiaolei Zhu, Rangaramanujam M Kannan, Dimitrios Kapogiannis, Norman J Haughey, Rana Rais, Barbara S Slusher   +16 more
openaire   +1 more source

Abstract A59: A tumor supressor role for nSMase2 in triple negative breast cancer

Cancer Immunology Research, 2022
Abstract PURPOSEIn this study, we assess a putative tumor suppressor role for neutral sphingomyelinase-2 (nSMase2) in triple negative breast cancer (TNBC) and determine if nSMase2 effects are through cell intrinsic or extrinsic mechanisms.
Andrew E Resnick, Fabiola N Valazquez, Samia Mohammed, Joseph Bonica, Danielle Guida, Victoria Alvarado, Deanna M Peperno, Yusuf A Hannun, Christopher J Clarke   +8 more
openaire   +1 more source

Evidence for coordination of lysosomal (ASMase) and plasma membrane (NSMase2) forms of sphingomyelinase from mutant mice [PDF]

FEBS Letters, 2012
NSMase2 is associated to the plasma membrane, whereas ASMase is predominantly lysosomal; both hydrolyze sphingomyelin (SM) to ceramide and phosphocholine. Although SM accumulated in both ASMase−/− and fro/fro (NSMase2−/−) fibroblasts, the reduction of ceramides was more dramatic in fro/fro cells.
Qin, Jingdong, Dawson, Glyn
exaly   +3 more sources

α2,6-Sialylation promotes hepatocellular carcinoma cells migration and invasion via enhancement of nSmase2-mediated exosomal miRNA sorting

Journal of Physiology and Biochemistry, 2022
Exosomes have a critical role in the intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). Recently, our group showed that α2, 6-sialylation played an important role in the proliferation- and migration-promoting effects of cancer-derived exosomes. However, the molecular basis remains elusive.
Liping Wang, Xixi Chen, Fanxu Meng, Tianmiao Huang, Shujing Wang, Zhichao Zheng, Guoliang Zheng, Wenli Li, Jianing Zhang, Yubo Liu   +9 more
openaire   +2 more sources

Neutral sphingomyelinase 2 (nSMase2) is the primary neutral sphingomyelinase isoform activated by tumour necrosis factor-α in MCF-7 cells [PDF]

Biochemical Journal, 2011
Activation of N-SMase (neutral sphingomyelinase) is an established part of the response of cytokines such as TNF (tumour necrosis factor)-α. However, it remains unclear which of the currently cloned N-SMase isoforms (nSMase1, nSMase2 and nSMase3) are responsible for this activity.
Christopher Clarke, Yusuf Hannun, Hannun Yusuf A   +2 more
exaly   +3 more sources

Endoplasmic reticulum stress-mediated inhibition of NSMase2 elevates plasma membrane cholesterol and attenuates NO production in endothelial cells

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2012
Chronic exposure of blood vessels to cardiovascular risk factors such as free fatty acids, LDL-cholesterol, homocysteine and hyperglycemia can give rise to endothelial dysfunction, partially due to decreased synthesis and bioavailability of nitric oxide (NO). Many of these same risk factors have been shown to induce endoplasmic reticulum (ER) stress in
Ruchi, Chaube, Vasantha Madhuri, Kallakunta, Michael Graham, Espey, Ryan, McLarty, Adam, Faccenda, Sirinart, Ananvoranich, Bulent, Mutus   +6 more
openaire   +2 more sources